scholarly journals Interactions of brain, blood, and CSF: a novel mathematical model of cerebral edema

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Omer Doron ◽  
Yuliya Zadka ◽  
Ofer Barnea ◽  
Guy Rosenthal
Keyword(s):  
Mathematical Model ◽  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Subarachnoid Space ◽  
Bulk Flow ◽  
Brain Barrier ◽  
Brain Swelling ◽  
Blood Brain ◽  
Rapid Injection ◽  
Volume Curve

Abstract Background Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model’s ability to depict changes in cerebral physiology associated with cerebral edema. Methods We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB). Results The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. Conclusions The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury.

scholarly journals The Neuroprotective Effects of Necrostatin-1 on Subarachnoid Hemorrhage in Rats Are Possibly Mediated by Preventing Blood–Brain Barrier Disruption and RIP3-Mediated Necroptosis

2019 ◽  
Vol 28 (11) ◽  
pp. 1358-1372 ◽  
Author(s):  
Jingsen Chen ◽  
Hanghuang Jin ◽  
Hangzhe Xu ◽  
Yucong Peng ◽  
Liyong Jie ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Brain Barrier ◽  
New Drugs ◽  
Brain Barrier ◽  
Lesion Volume ◽  
Brain Swelling ◽  
Neuroprotective Effects ◽  
Pharmaceutical Therapy ◽  
Blood Brain

Despite the substantial efforts to elucidate the role of early brain injury in subarachnoid hemorrhage (SAH), an effective pharmaceutical therapy for patients with SAH continues to be unavailable. This study aims to reveal the role of necroptosis after SAH, and explore whether the disruption of the blood–brain barrier (BBB) and RIP3-mediated necroptosis following SAH in a rat SAH model are altered by necrostatin-1 via its selective inhibition of receptor-interacting protein kinase 1 (RIP1). Sixty-five rats were used in the experiments. The SAH model was established using endovascular perforation. Necrostatin-1 was intracerebroventricularly injected 1 h before SAH induction. The neuroprotective effects of necrostatin-1 were evaluated with multiple methods such as magnetic resonance imaging (MRI) scanning, immunohistochemistry, propidium iodide (PI) labeling, and western blotting. Pretreatment with necrostatin-1 attenuated brain swelling and reduced the lesion volume on T2 sequence and ventricular volume on MRI 72 h after SAH induction. Albumin leakage and the degradation of tight junction proteins were also ameliorated by necrostatin-1 administration. In addition, necrostatin-1 decreased the number of PI-positive cells in the basal cortex, reduced the levels of the RIP3 and MLKL proteins, and inhibited the production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Based on the findings from the present study, the selective RIP1 inhibitor necrostatin-1 functioned as a neuroprotective agent after SAH by attenuating brain swelling and BBB disruption. Moreover, the necrostatin-1 pretreatment prevented SAH-induced necroptosis by suppressing the activity of the RIP3/MLKL signaling pathway. These results will provide insights into new drugs and pharmacological targets to manage SAH, which are worth further study.

scholarly journals Cerebral Edema Formation After Stroke: Emphasis on Blood–Brain Barrier and the Lymphatic Drainage System of the Brain

2021 ◽  
Vol 15 ◽  
Author(s):  
Sichao Chen ◽  
Linqian Shao ◽  
Li Ma
Keyword(s):  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Lymphatic System ◽  
Vasogenic Edema ◽  
Lymphatic Vessels ◽  
Drainage System ◽  
Brain Barrier ◽  
Edema Formation ◽  
Blood Brain ◽  
The Brain

Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion and may also result in transtentorial herniation. As a physical and biochemical barrier between the peripheral circulation and the central nervous system (CNS), the blood–brain barrier (BBB) plays a vital role in maintaining the stable microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the dysfunction of the BBB results in increased paracellular permeability, directly contributing to the extravasation of blood components into the brain and causing cerebral vasogenic edema. Recent studies have led to the discovery of the glymphatic system and meningeal lymphatic vessels, which provide a channel for cerebrospinal fluid (CSF) to enter the brain and drain to nearby lymph nodes and communicate with the peripheral immune system, modulating immune surveillance and brain responses. A deeper understanding of the function of the cerebral lymphatic system calls into question the known mechanisms of cerebral edema after stroke. In this review, we first discuss how BBB disruption after stroke can cause or contribute to cerebral edema from the perspective of molecular and cellular pathophysiology. Finally, we discuss how the cerebral lymphatic system participates in the formation of cerebral edema after stroke and summarize the pathophysiological process of cerebral edema formation after stroke from the two directions of the BBB and cerebral lymphatic system.

scholarly journals Application of Blood-Brain Barrier Permeability Imaging in Global Cerebral Edema

2016 ◽  
Vol 37 (9) ◽  
pp. 1599-1603 ◽  
Author(s):  
J. Ivanidze ◽  
O.N. Kallas ◽  
A. Gupta ◽  
E. Weidman ◽  
H. Baradaran ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Cerebral Edema ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

scholarly journals EphrinB2 Activation Enhances Vascular Repair Mechanisms and Reduces Brain Swelling After Mild Cerebral Ischemia

2017 ◽  
Vol 37 (5) ◽  
pp. 867-878 ◽  
Author(s):  
Adnan Ghori ◽  
Florian B. Freimann ◽  
Melina Nieminen-Kelhä ◽  
Irina Kremenetskaia ◽  
Karen Gertz ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Blood Brain Barrier ◽  
Major Complication ◽  
Artery Occlusion ◽  
Brain Barrier ◽  
Tyrosine Kinase Receptor ◽  
Vascular Repair ◽  
Brain Swelling ◽  
Blood Brain ◽  
Repair Mechanisms

Objective— Cerebral edema caused by the disruption of the blood–brain barrier is a major complication after stroke. Therefore, strategies to accelerate and enhance neurovascular recovery after stroke are of prime interest. Our main aim was to study the role of ephrinB2/EphB4 signaling in mediating the vascular repair and in blood–brain barrier restoration after mild cerebral ischemia occlusion/reperfusion. Approach and Results— Here, we show that the guidance molecule ephrinB2 plays a key role in neurovascular protection and blood–brain barrier restoration after stroke. In a focal stroke model, we characterize the stroke-induced damage to cerebral blood vessels and their subsequent endogenous repair on a cellular, molecular, and functional level. EphrinB2 and its tyrosine kinase receptor EphB4 are upregulated early after stroke by endothelial cells and perivascular support cells, in parallel to their reassembly during neurovascular recovery. Using both retroviral and pharmacological approaches, we show that the inhibition of ephrinB2/EphB4 signaling suppresses post-middle cerebral artery occlusion neurovascular repair mechanisms resulting in an aggravation of brain swelling. In contrast, the activation of ephrinB2 after brain ischemia leads to an increased pericyte recruitment and increased endothelial–pericyte interaction, resulting in an accelerated neurovascular repair after ischemia. Conclusions— We show that reducing swelling could result in improved outcome because of reduction in damaged brain tissue. We also identify a novel role for ephrinB2/EphB4 signaling in the maintenance of the neurovascular homeostasis and provide a novel therapeutic approach in reducing brain swelling after stroke.

scholarly journals Blood–brain barrier, bulk flow, and interstitial clearance in epilepsy

2016 ◽  
Vol 260 ◽  
pp. 118-124 ◽  
Author(s):  
Nicola Marchi ◽  
Manoj Banjara ◽  
Damir Janigro
Keyword(s):  
Blood Brain Barrier ◽  
Bulk Flow ◽  
Brain Barrier ◽  
Blood Brain
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